On Apple iMac platform you can easily zoom in and out of the desktop using finger motions on your mouse much like you would on an iPhone. If your eyes have problems with font sizes I suggest it. You will not need to "change font sizes" someone else set. You'll just zoom in out when some app is hard to read (instead of fighting fonts and sizing issues), and your done

I don't have problems with "font proportion" that your mentioning on iMac - but i think that's totally preferential I have no reason to suspect you would feel the same way.

What you should worry about is that if you "tamper" with fonts you might break them (and mathematica installation, even your OS installtion). fonts are "critical" if you mess them up you won't even boot. also if you have MISSING FONTS in mathematica - you might see all but one symbol in an equation and "be fooled" (meaning, Mathematica fonts are a fine balance of never allowing a "vanishing act", whereas using google chrome web browser, you might not see many symbols on a page, have no warning they are missing, and that is considered "normal", for mathematica - it's designed to "not let that happen"). mess with the fonts - you might trip up mathematica and have occasionally missing fonts, which is worse.

I would ask Wolfram support before doing any font hacks.

But remember - I said "magic mouse" and zoom (available by 3rd parties not as good on Win10)

I have awful problems on a PC reading text on Win10 (fonts are so small and large and "pre-conceived"). I can't do it. That's why I love my finger motion zooms.

Yes i was testing if it had to do with those settings. It persists after rebooting.

All my other applications look perfectly fine.

I set my scale of mathematica to 75% else it is even worse the normal font then is way to large compared to the rest of my screen. But the relative small scaling of these labels in manipulate seem to be not affected by that.

If I set my system scale and layout to 100% everything is correctly in proportion. However than everything is so small i cant even read anything. So it seems that everything in the mathematica application is scaled correctly by the system scaling but not the manipulate labels.